Infection with Legionella micdadei remains a serious problem at the University of Pittsburgh. As methods for serology and culture of this organism improve, more cases worldwide are being reported. This project will explore normal host defenses against Legionella micdadei. In particular human neutrophil, monocyte, and monocyte derived macrophage interactions with this organism will be examined and the effects of specific antibody and complement on the relationships will be elucidated. The mechanism(s) of intracellular survival, when it occurs, will be avidly pursued. Since this organism is primarily a cause of morbidity and mortality to individuals on immunosuppressive agents, the in vitro effects of these agents on normal phagocyte response to L. micdadei will be clarified. Mortality due to infection with this organism remains high, despite antibiotics that are effective in vitro. Antimicrobial interactions with host phagocytes and L. micdadei will be explored with special attention paid to the effects on intracellular killing or growth. Agents that augment phagocytic cidal capabilities will also be studied in vitro to determine their possible usefulness in this disease. Lastly, normal host response to this organism will be compared to that of L. pneumophila. These studies may explain the differing host susceptibilities to these two agents and may reveal fundamental characteristics of immunity to bacterial infection.